Trade-offs are inherent to biochemical networks governing diverse cellular functions, from gene expression to metabolism. Yet, trade-offs between fluxes of biochemical reactions in a metabolic network have not been formally studied. Here, we introduce the concept of absolute flux trade-offs and devise a constraint-based approach, termed FluTO, to identify and enumerate flux trade-offs in a given genome-scale metabolic network. By employing the metabolic networks of Escherichia coli and Saccharomyces cerevisiae, we demonstrate that the flux trade-offs are specific to carbon sources provided but that reactions involved in the cofactor and prosthetic group biosynthesis are present in trade-offs across all carbon sources supporting growth. We also show that absolute flux trade-offs depend on the biomass reaction used to model the growth of Arabidopsis thaliana under different carbon and nitrogen conditions. The identified flux trade-offs reflect the tight coupling between nitrogen, carbon, and sulphur metabolisms in leaves of C₃ plants. Altogether, FluTO provides the means to explore the space of alternative metabolic routes reflecting the constraints imposed by inherent flux trade-offs in large-scale metabolic networks.

• PMID: 34893666
• DOI full text
• PMC full text
• PubMed
• PubTator

Reference Type

Journal Article | Research Support, Non-U.S. Gov't

Authors

Hashemi S, Razaghi-Moghadam Z, Nikoloski Z

Primary Lit For

Additional Lit For

Review For